6alpha-methyl-delta1, 4-pregnadien-17alpha-ol-3, 20-dione and esters thereof



3, 3,965 Umted States Patent Office 311,

The process for the production of the above novel 3,203,965 compoundsmay be illustrated by the following equation: 6u-R1 ETHYL-A-PREGNADIEN-IVa-OL-SflD-DIONE AND ESTERS THEREOF a CH3 Howard J. Ringoldand George Rosenkranz, Mexico 4 City, Mexico, assignors, by mesneassignments, to Syn- 5 1.... tex Corporation, a corporation of Panama NoDrawing. Filed June 25, 1958, Ser. No. 744,347 Claims priority,application Mexico, May 14, 1958,

50,998 I 4 Claims. (Cl. 260-3974) I dehydrogenation This application is-a continnationdn-part of our co- 0: 83, 35 0- pending applicationSerial No. 709,795, tiled January 20, 5

1958, now abandoned. on,

The present invention relates to novel cyclopentano- I h above ti .Rrepresents the same groups Phfinanfllffle mpounds. as heretofore setforth.

More particularly the present invention relates to the I practicing theprocess above Outlined g p novel 6wmethyl-AlLpregnadiemlkrill-330410116and its A -pregnen-l7a-ol-3,20-dione or an ester of the characterhydrocarbon carboxylic acid esters f less than 12 carbon hereinbeforeset forth is refluxed with selenium dioxide atoms. The compounds of thepresent invention and esi h presence f tibuttanol and f mbfly a t l ti'P y esters 0f y -P amount of pyridine. The reaction product afterconvenare y vahlable Progestatioflal hormones tional purification is thecorresponding 6a-methy1A having the same type of valuable action asprogesterone pregn-adien-rl7a-ol-3,20-dione or ester. -In place of sebutto a surprisingly greater amount. lenium dioxide other dehydrogenatingagents may the used :In our US. patent application Serial No. 679,762,fi led to produce the Cl,2 double :bond as for example chlora- August22, 1957, there is disclosed the production of 6anil in the presence ofxylene or n-amyl alcohol or a micromethyl-M-pregnen-l7u-ol 3,20-dioneand the hydrocarbon biological treatment such as disclosed in US. PatentNo. carboxylic acid esters thereof. 2,837,464, granted June 3,1958.

In accordance with the present invention it has been When the endproduct is an ester of 6ormethy1-A discovered that dehydrogenation ofGu-methyl-A -pregpregnadien-17a-ol-3,20 1ione, this ester may heconvennen-l7a-ol-3,20-dione or the hydrocarbon carboxylic acidventionally saponi-fied with alkali to give the free comesters thereofwith selenium dioxide for example propound and conversely the freecompound may be convenduce-s the potent progestational hormones of thepresent tiona-l'ly esterified using Well known methods for the inventionpreviously referred to. The novel progestaesterification of tertiarysteroid alcohols. tional hormones of the present invention may be illus-The following specific examples serve to illustrate but trated by thefollowing formula: are not intended to limit the present invention:

Example 1 1 g. of the acetate of 6a-methyl-17-hydroxyprogesterone(acetate of 6a-methyl-A -pregnen-17a-o1-3,2O-dione) 40 was refluxed for72 hours in 50 cc. of t-butanol, together OH; with 0.4 g. of seleniumdioxide and 014 cc. of pyridine 0 under a nitrogen atmosphere. Thereaction product was I.... filtered and the residue was washed with 20cc. of hot t-butanol. The washings and the filtrate were combined l andthe solvent evaporated under reduced pressure. The

residue was dissolved in acetone, activated carbon was added .and theacetone solution refluxed for an hour, The

product was then filtered to remove carbon and the ace- 0 toneevaporated. After conventional chromatography,

: using an alumina filled column and benzene, benzeneether as solvents,the product obtained was the acetate of 6or-methyl-A -pregnadien-i17or-ol-3,QO-dione.

Example I] When the method of Example I was repeated using as a startingmaterial the free 6a-metl1y1-17-hydroxyproges- In the above formula Rrepresents hydrogen or a hydroterone, the ppoduct obtained was m f 1,4

carbon carboxylic acid ester group of less than 12 carbon q7 n 1 3;2 n il fi of hi atoms. ThESB ester groups as wall known in the steroid oundusing conventional acylatign procedures for the art y $911 died ofunsaturated, stP-aighi OI bIanChBd 17u-hydroxy group, i.e., acidanhydrides or acyl chlorides, chain aliphatic, cyclic or mixedcyclic-aliphatic and may esterification medium comprising thecorresponding acid be conventionally substituted as by halogen ormethoxy. and/or an inert solvent such as dioxane; acid catalyst Typicalester groups are acetate, propion-atc, cyclopentyl- (p-t-oluenesulfonicacid) gave the corresponding il7-KII1OI10 proprionate, capro-ate,enanthate, benzoate, trimethylesters of hydrocarbon carboxylic acids ofless than 12 caracetate, etc, bon atoms. 'Ihus prepared were thepropionate, cyclw 3 a pentylpropionate, benzoate, butyrate, caproate andenarlwherein R is selected from the group consisting of hydro- 1211818.7 v 7 gen and a hydrocarbon carboxylic acyl group of =1ess than ExampleI 12 carbon atoms.

2. 6namethy1-A -pregn-adien 17a-o1-3,20-dione. of 't I was repeated 5 as5 3. The hydrocarbon carboxylic acid esters of flan-methylstartlngmatenal, the propronate, cyclopentylpropronate, AM Jpregna ii-61147 20dione benzoate, butyrate and enanthate or 6a-methy1-17-hy- 4 The acetateof f6a methy1 A1,4 pregnadiem17a ol droxyprogesterone. The correspondmgesters of 6oz- 6 methyl-A -pregnadien-17a-ol-3,2O-dione were preparedlone g i t those of Example 10 References Cited by the Examiner e 0 am:I '1. A'compound having the following formula: UNITED STATES PATENTS2,579,479 I12/5 1' Djerassi 260-3914 15 I OTHER REFERENCES JAC-S, vol.78, Feb. 20, 1956, pages 8168 19.

LEWIS G'OTIS, Primary Examiner.

I 20 B. LANHAM, LESLIE H. GASTON, Examiners.

1. A COMPOUND HAVING THE FOLLOWING FORMULA: